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In this paper, the authors study a class of general mean-field BDSDEs whose coefficients satisfy some stochastic conditions. Specifically, the authors prove the existence and uniqueness theorem of solution under stochastic Lipschitz condition and obtain the related comparison theorem. Besides, the authors further relax the conditions and deduce the existence theorem of solutions under stochastic linear growth and continuous conditions, and the authors also prove the associated comparison theorem. Finally, an asset pricing problem is discussed, which demonstrates the application of the general mean-field BDSDEs in finance.

Autosomal recessive deafness 9, caused by mutations of the OTOFgene, is characterised by congenital or prelingual, severe-to-complete, bilateral hearing loss. However, no pharmacological treatment is currently available for congenital deafness. In this Article, we report the safety and efficacy of gene therapy with an adeno-associated virus (AAV) serotype 1 carrying a human OTOFtransgene (AAV1-hOTOF) as a treatment for children with autosomal recessive deafness 9.

Transient impact loads can easily cause structural damage and destruction, especially for composite structures that are susceptible to collisions. An accurate impact source localization method is crucial for evaluating the potential structure damage location. The impact response signals, on the other hand, contain varying degrees of high- and low-frequency noise, and the structure is not limited to a single dimension. In this article, the robust localization method with empirical mode decomposition combined wavelet denoising (EMD-WD) and multi-output support vector regression (MSVR) is proposed. Following the achievement of intrinsic mode function (IMF) of distinct frequency bands, the last order IMF is abandoned to filter the low-frequency disturbance. Following that, the discrete wavelet transform is used to treat high-frequency noise. Then, multidimensional features of impact responses, including time domain (TT), frequency domain (FF), time–frequency domain (TF), and distance domain (DD), are extracted. Finally, MSVR trained with multidimensional feature vectors is used to predict various impact location coordinate values. The results on plate structure and cylinder composite monitoring data prove that the proposed method can realize acceptable localization performance on both the 2-D and 3-D structures compared with other methods, with certain abilities to resist noise interference.

Gene therapy is a promising approach for hereditary deafness. We recently showed that unilateral AAV1-hOTOF gene therapy with dual adeno-associated virus (AAV) serotype 1 carrying human OTOFtransgene is safe and associated with functional improvements in patients with autosomal recessive deafness 9 (DFNB9). The protocol was subsequently amended and approved to allow bilateral gene therapy administration. Here we report an interim analysis of the single-arm trial investigating the safety and efficacy of binaural therapy in five pediatric patients with DFNB9. The primary endpoint was dose-limiting toxicity at 6 weeks, and the secondary endpoint included safety (adverse events) and efficacy (auditory function and speech perception). No dose-limiting toxicity or serious adverse event occurred. A total of 36 adverse events occurred. The most common adverse events were increased lymphocyte counts (6 out of 36) and increased cholesterol levels (6 out of 36). All patients had bilateral hearing restoration. The average auditory brainstem response threshold in the right (left) ear was >95 dB (>95 dB) in all patients at baseline, and the average auditory brainstem response threshold in the right (left) ear was restored to 58 dB (58 dB) in patient 1, 75 dB (85 dB) in patient 2, 55 dB (50 dB) in patient 3 at 26 weeks, and 75 dB (78 dB) in patient 4 and 63 dB (63 dB) in patient 5 at 13 weeks. The speech perception and the capability of sound source localization were restored in all five patients. These results provide preliminary insights on the safety and efficacy of binaural AAV gene therapy for hereditary deafness. The trial is ongoing with longer follow-up to confirm the safety and efficacy findings. Chinese Clinical Trial Registry registration: ChiCTR2200063181.

Kupffer cells, the liver tissue resident macrophages, are critical in the detection and clearance of cancer cells. However, the molecular mechanisms underlying their detection and phagocytosis of cancer cells are still unclear. Using in vivo genome-wide CRISPR-Cas9 knockout screening, we found that the cell-surface transmembrane protein ERMAP expressed on various cancer cells signaled to activate phagocytosis in Kupffer cells and to control of liver metastasis. ERMAP interacted with β-galactoside binding lectin galectin-9 expressed on the surface of Kupffer cells in a manner dependent on glycosylation. Galectin-9 formed a bridging complex with ERMAP and the transmembrane receptor dectin-2, expressed on Kupffer cells, to induce the detection and phagocytosis of cancer cells by Kupffer cells. Patients with low expression of ERMAP on tumors had more liver metastases. Thus, our study identified the ERMAP–galectin–9-dectin-2 axis as an ‘eat me’ signal for Kupffer cells.

An altered proteome in lymph nodes often suggests abnormal signaling pathways that may be associated with diverse lymphatic disorders. Current clinical biomarkers for histological classification of lymphomas have encountered many discrepancies, particularly for borderline cases. Therefore, we launched a comprehensive proteomic study aimed to establish a proteomic landscape of patients with various lymphatic disorders and identify proteomic variations associated with different disease subgroups. In this study, 109 fresh-frozen lymph node tissues from patients with various lymphatic disorders (with a focus on Non-Hodgkin’s Lymphoma) were analyzed by data-independent acquisition mass spectrometry. A quantitative proteomic landscape was comprehensively characterized, leading to the identification of featured protein profiles for each subgroup. Potential correlations between clinical outcomes and expression profiles of signature proteins were also probed. Two representative signature proteins, phospholipid-binding proteins Annexin A6 (ANXA6) and Phospholipase C Gamma 2 (PLCG2), were successfully validated via immunohistochemistry. We also evaluated the capability of acquired proteomic signatures to segregate multiple lymphatic abnormalities and identified several core signature proteins, such as Sialic Acid Binding Ig Like Lectin 1 (SIGLEC1) and GTPase of immunity-associated protein 5 (GIMAP5). In summary, the established lympho-specific data resource provides a comprehensive map of protein expression in lymph nodes during multiple disease states, thus extending the existing human tissue proteome atlas. Our findings will be of great value in exploring protein expression and regulation underlying lymphatic malignancies, while also providing novel protein candidates to classify various lymphomas for more precise medical practice.

Gold nanoparticles (AuNPs) are one of the most commonly used reagents in colloidal science and biosensor technology. In this work, we first compared AuNPs prepared using four different reducing agents including citrate, glucose, ascorbate, and 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid (HEPES). At the same absorbance at the surface plasmon peak of 520–530 nm, citrate-AuNPs and glucose-AuNPs adsorbed more DNA and achieved higher affinity to the adsorbed DNA. In addition, citrate-AuNPs had better sensitivity than glucose-AuNPs for label-free DNA detection. Then, using citrate-AuNPs, the effect of aging was studied by incubation of the AuNPs at 22 °C (room temperature) and at 4 °C for up to 6 months. During aging, the colloidal stability and DNA adsorption efficiency gradually decreased. In addition, the DNA sensing sensitivity using a label-free method also dropped around 4-fold after 6 months. Heating at boiling temperature of the aged citrate-AuNPs could not rejuvenate the sensing performance. This study shows that while citrate-AuNPs are initially better than the other three AuNPs in their colloid properties and sensing properties, this edge in performance might gradually decrease due to constantly changing surface properties caused from the aging effect.

Based on the surface plasmon resonance imaging (SPRi) instrument, we established a new method of analyzing morphine in urine by processing a calibration curve. According to an inhibition immunoassay, gradient concentration of morphine and morphine-BSA fixed on the chip competitively combine with morphine antibody on the chip. Given the three mathematical models, the data of SPRi signals generated from SPRi with morphine was processed to obtain the calibration curve. Ultrafiltration was used to pretreat blank urine samples with adding morphine, and then investigated the advantages and disadvantages of each model. With a limit detection of 6.57 ng·mL−1, the method and mathematical models can provide robust support for SPRi sensors used in further environmental detection, such as the epidemiological study of sewage.

Forward Freight Agreements (FFAs) are consequential derivatives for risk hedging in the shipping market. This paper presents the first empirical study of convenience yield in the shipping market with a sample of C3 (Tubarao to Qingdao) and C5 (Western Australia to Qingdao) FFAs from 2013 to 2023. First, single-factor and two-factor models are constructed to analyze the random behavior of freight rates in the shipping market, and the existence of convenience yield is empirically tested. The results provide evidence of the existence of convenience yield in the shipping market, with its stochastic variation being a critical factor in shaping the term structure characteristics of FFAs. Second, an ARMAX model is developed for the freight rate index, and the predictive role of the estimated convenience yield and its difference in spot freight rates is analyzed by operating the two-factor model. The findings reveal a significant predictive effect of convenience yield and its difference on spot freight rates. Last but not least, this study emphasizes the importance of convenience yield as a crucial parameter in the shipping market, particularly regarding the transportation of bulk commodities. Changes in the supply and demand of bulk commodities directly impact the fluctuations in shipping market capacity and convenience yield. This study delivers a new explanatory perspective for price formation in the shipping market and is highly valuable for risk management in this sector.

Due to the increasing environmental pollution caused by human activities, environmental remediation has become an important subject for humans and environmental safety. The quest for beneficial pathways to remove organic and inorganic contaminants has been the theme of considerable investigations in the past decade. The easy and quick separation made magnetic solid-phase extraction (MSPE) a popular method for the removal of different pollutants from the environment. Metal–organic frameworks (MOFs) are a class of porous materials best known for their ultrahigh porosity. Moreover, these materials can be easily modified with useful ligands and form various composites with varying characteristics, thus rendering them an ideal candidate as adsorbing agents for MSPE. Herein, research on MSPE, encompassing MOFs as sorbents and Fe3O4as a magnetic component, is surveyed for environmental applications. Initially, assorted pollutants and their threats to human and environmental safety are introduced with a brief introduction to MOFs and MSPE. Subsequently, the deployment of magnetic MOFs (MMOFs) as sorbents for the removal of various organic and inorganic pollutants from the environment is deliberated, encompassing the outlooks and perspectives of this field.

The extension of green and sustainable materials in the preparation of heterogeneous catalysts for organic transformations has increased over the past few decades. Because of their unique and intriguing physical and chemical properties, two-dimensional (2D) nanostructured materials have attracted widespread attention and have been used in a variety of applications, such as catalysis, electronics, and energy storage. A promising pathway to enhance the performance of 2D nanomaterials is their coupling with other functional materials to form heterogeneous or hybrid structures. Herein, we discuss the use of 2D-based nanostructured catalysts for enhancing organic transformations and highlight selected examples to demonstrate the synthesis, advantages, challenges, efficiency, and reusability of the introduced heterogeneous catalysts for cross-coupling and reduction reactions.

•An electrochemical etching bench is built to etch Inconel 718 plates.•The effects of etchant concentration and temperature on etching rate are investigated.•Ultrasonic waves from two directions are added to the electrochemical etching process.•The surface roughness of etched plates for each working condition was measured.•Microscopic observation of etched plates for each working condition was carried out.

Metal organic framework (MOF)-derived nanocatalysts on various nanostructured supports are generally efficient heterogeneous catalysts employable for organic transformations. Herein, nickel Prussian blue (PB) nanoparticles were deployed to form NiFe 2 O 4 nanocatalysts supported on 2D molybdenum disulfide (MoS 2) through a facile heat treatment. NiFe 2 O 4 nanocatalysts could be uniformly dispersed on the high-specific-area MoS 2 surface, representing a highly efficient, inexpensive, and magnetically recoverable nanocomposite catalyst. The semiconductor property of MoS 2 ensures a high electric conductivity, thus enhancing electron transfer between the reductant and the reactant. Furthermore, the strong magnetic characteristics enable its convenient separation from the reaction mixture. NiFe 2 O 4 nanoparticles on MoS 2 -supported produces multiple electron transfer pathways and overcomes known drawbacks of catalytic methods that use metals alone, endowing long-term cycle stability. Overall, MoS 2 /NiFe 2 O 4 exhibited an excellent catalytic activity and high yields in the reduction of nitrobenzene in water, maintained even after five cycles. [ABSTRACT FROM AUTHOR]

Myosin VI（MYO6） is an unconventional myosin that is vital for auditory and vestibular function. Pathogenic variants in the human MYO6gene cause autosomal-dominant or -recessive forms of hearing loss. Effective treatments for Myo6mutation causing hearing loss are limited. We studied whether adeno-associated virus (AAV)-PHP.eB vector-mediated in vivodelivery of Staphylococcus aureusCas9 (SaCas9-KKH)-single-guide RNA (sgRNA) complexes could ameliorate hearing loss in a Myo6WT/C442Ymouse model that recapitulated the phenotypes of human patients. The in vivoediting efficiency of the AAV-SaCas9-KKH-Myo6-g2 system on Myo6C442Yis 4.05% on average in Myo6WT/C442Ymice, which was ∼17-fold greater than editing efficiency of Myo6WTalleles. Rescue of auditory function was observed up to 5 months post AAV-SaCas9-KKH-Myo6-g2 injection in Myo6WT/C442Ymice. Meanwhile, shorter latencies of auditory brainstem response (ABR) wave I, lower distortion product otoacoustic emission (DPOAE) thresholds, increased cell survival rates, more regular hair bundle morphology, and recovery of inward calcium levels were also observed in the AAV-SaCas9-KKH-Myo6-g2-treated ears compared to untreated ears. These findings provide further reference for in vivogenome editing as a therapeutic treatment for various semi-dominant forms of hearing loss and other semi-dominant diseases.

ASBTARCTStructures with energy supply capacity are an important part of lifeline engineering. Post-disaster assessment is therefore vital to assess the economic losses caused by the collapse of such structures and is an integral part of the overall post-disaster assessment. The identification of structures in synthetic aperture radar (SAR) imagery is mostly influenced by buildings, exposed rocks and riverbeds, because of the similar scattering intensity effects. In this letter, a new spatial reasoning method is proposed based on spatial and morphological feature parameters to identify isolated structures with an ordered distribution in SAR imagery. The wind power generation base in the north-western part of the city of Yumen, Gansu province, China, is taken as the research area. Numerous wind power generation facilities, which are important power sources in north-western China, are found in this area. The recognition accuracy of the proposed method for structures in this area is 98.31%. Compared with the traditional method, the recognition rate for structures is improved by 35.59%. The ‘distance deviation risk’ evaluation index is also proposed to evaluate the deviation between the recognition results and the actual ground objects. Overall, the proposed method can more accurately identify the structures in SAR imagery.

ABSTRACTDue to the casualties and economic losses that can be caused by building collapse after an earthquake, building damage assessment is a very important part of earthquake disaster evaluation. As a result of the advantages of polarimetric synthetic aperture radar (PolSAR) imaging, both the accuracy and speed of the damage assessment can be guaranteed in the process of building damage identification using a single post-earthquake PolSAR image. The number of collapsed buildings is usually overestimated when adopting the traditional method, which is because the scattering mechanism is similar to that of intact oriented buildings. In view of this, the variable coefficient of angle domains based on the Fourier amplitude spectrum parameter (CV_AFI) is proposed to ameliorate the damaged building overestimation. By combining the improved Yamaguchi four-component decomposition method with the CV_AFI parameter, the proposed method can be used to extract building damage information from a single PolSAR image. With the Ms 7.1 Yushu earthquake in China as the research case, compared with the traditional method, the producer’s accuracy of the proposed method for undamaged buildings was increased by 38.87%. The proposed method can obtain a higher accuracy of building damage information extraction and significantly reduce building damage overestimation.

Self-assembly is a powerful means to fabricate multifunctional smart nanotheranostics. However, the complicated preparation, toxicity of responsive carriers, and low loading efficiency of drug cargo hinder the outcome. Herein, we developed a responsive carrier-free noncovalent self-assembly strategy of a metallized Au(III) tetra-(4-pyridyl) porphine (AuTPyP) anticancer drug for the preparation of a heat/acid dual-stimulated nanodrug, and it generated a better photothermal effect than monomers under irradiation. The photothermal effect promoted the protonation of the hydrophobic pyridyl group and the following release into tumorous acidic microenvironments. With cRGD modification, the released drug induced the aggravation of intracellular reactive oxygen species (ROS) via the activity inhibition of thioredoxin reductase (TrxR) for synergistic chemo-photothermal therapy of tumors.

•Bicarbonate pool efficiently support CO2capture and microalgae cultivation.•Spirulina platensiswith high pH tolerant up to 12.5 was screened.•Bicarbonate pool with bicarbonate concentration up to 0.5 M and pH up to12.5.•Direct capture CO2with microalgae cultivation may be driven by renewable energy.

To investigate the association of infant sleep and sleep trajectories through the first year of life with infant neurodevelopment.

While maternal exposure to high metal levels during pregnancy is an established risk factor for birth defects, the role of paternal exposure remains largely unknown. We aimed to assess the associations of prenatal paternal and maternal metal exposure and parental coexposure with birth defects in singletons. This study conducted within the Jiangsu Birth Cohort recruited couples in early pregnancy. We measured their urinary concentrations for 25 metals. A total of 1675 parent–offspring trios were included. The prevalence of any birth defects among infants by one year of age was 7.82%. Paternal-specific gravity-corrected urinary concentrations of titanium, vanadium, chromium, manganese, cobalt, nickel, copper, and selenium and maternal vanadium, chromium, nickel, copper, selenium, and antimony were associated with a 21–91% increased risk of birth defects after adjusting for covariates. These effects persisted after mutual adjustment for the spouse’s exposure. Notably, when assessing the parental mixture effect by Bayesian kernel machine regression, paternal and maternal chromium exposure ranked the highest in relative importance. Parental coexposure to metal mixture showed a pronounced joint effect on the risk of overall birth defects, as well as for some specific subtypes. Our findings suggested a couple-based prevention strategy for metal exposure to reduce birth defects in offspring.

The absolute configurations of the three unknown chiral centers in vinylamycin were predicted according to the structural comparison with microtermolide A and rakicidin A, and then total syntheses of vinylamycin were applied to determine the three unknown chiral centers as 14R, 15R, and 16S.

Background

Abstract：

The therapeutic advancements over the last decade have dramatically improved the prognosis and decreased the mortality of acute promyelocytic leukemia (APL). Some patients still recur repeatedly, and the poor curative effect of some patients has become a challenging issue. Survival may be impacted by additional concurrent mechanisms linked to additional chromosome abnormalities (ACA) as a potential pathogenic factor. Therefore, to confirm the role of ACA, we retrospectively analyzed the characteristics and prognostic impact of ACA in a series of newly diagnosed APL patients with t(15;17)(q22;q21).

Background:Diffuse large B cell lymphoma (DLBCL) is common in the elderly group. New schedules are required due to the toxicity in classic chemotherapy regimens. Previous studies reported that non-germinal center B cell (non-GCB) subtype aggregates in elderly patients with abnormality in the activated B cell receptor signal and nuclear factor kappa-B pathway. We conducted a prospective trial to investigate the efficacy and safety of the ZR2-miniCHOP schedule (zanubrutinib, lenalidomide, rituximab, cyclophosphamide, vincristine, epirubicin and prednisone) in elder patients newly diagnosed with non-GCB DLBCL.

A key oxidizing agent for the chemical industry, wastewater treatment, and semiconductor development is hydrogen peroxide (H2O2). Electrochemical (EC) and photoelectrochemical (PEC) production of H2O2syntheses have been studied as promising alternatives to the unsustainable anthraquinone oxidation process and the H2and O2direct gas synthesis route. While cathodic O2reduction to produce H2O2draws more extensive attention than anodic water oxidation due to the higher obtained indicator of Faraday efficiency and production rate of H2O2, however, in the long term, using water as a raw material for water oxidation is a desirable procedure for the sustainable development of H2O2production. To inspire innovative ideas for boosting the H2O2yield in photo/electrocatalysis, we review recent advancements in EC/PEC H2O2production from experimental and computational points of view. The fundamental mechanism of the process, rational design of the electrode, and advanced engineering strategies for enhancement of H2O2production via a two-electron water oxidation reaction (2e–WOR) are thoroughly summarized. Furthermore, we discuss the hindrances and challenges of 2e–WOR, including all intermediates and competing reaction routes, integrate tandem device development, and the H2O2degradation issues for better addressing. 2e–WOR enables more excellent H2O2production rates with optimal efficiency.

Cardiogenesis is a tightly regulated dynamic process through a continuum of differentiation and proliferation events. Key factors and pathways governing this process remain incompletely understood. Here, we investigate mice hearts from embryonic day 10.5 to postnatal week 8 and dissect developmental changes in phosphoproteome-, proteome-, metabolome-, and transcriptome-encompassing cardiogenesis and cardiac maturation. We identify mitogen-activated protein kinases as core kinases involved in transcriptional regulation by mediating the phosphorylation of chromatin remodeling proteins during early cardiogenesis. We construct the reciprocal regulatory network of transcription factors (TFs) and identify a series of TFs controlling early cardiogenesis involved in cycling-dependent proliferation. After birth, we identify cardiac resident macrophages with high arachidonic acid metabolism activities likely involved in the clearance of injured apoptotic cardiomyocytes. Together, our comprehensive multi-omics data offer a panoramic view of cardiac development and maturation that provides a resource for further in-depth functional exploration.

Background: Potential of algal biomass for fuels, food, feed, and value-added chemicals through autotrophic and heterotrophic metabolic pathways has long been recognized. Existing downstream processing techniques, however, are not mature enough to overcome either techno-economic barriers or sustainability concerns, among which, energy-intensive microalgae harvesting is one of the biggest challenges. Biological microalgae harvesting has been demonstrated as the most promising technology in the near future that are economically viable and environmentally friendly at the same time. Methods: This paper critically reviews the current status and prospects of bioflocculation for microalgae harvesting. Approaches for microalgae bio-flocculation are summarized, factors that influence bio-flocculation of microalgae are indicated, and strategies for scaled-up applications are also discussed. Results: Microalgae bio-flocculation approaches include auto-flocculating algae-based, bacteria-based, filamentous fungibased, and plants extracts-based bio-flocculation. Type of flocculating microorganism, strain of target microalgae, and various co-culturing conditions could all influence microalgal bio-flocculation efficiency. Utilization of the bioflocculated algal biomass for fuel, food, feed, valued-added products, and for wastewater treatment are the two major strategies for scaled-up application of microalgae bio-flocculation in the future. Conclusion: Bio-flocculation of microalgae is a promising low-cost algae harvesting technology with unique advantages over traditional harvesting methods. Future studies should not only focus on improving bio-flocculation efficiencies under specific conditions, but should also investigate strategies for scaled-up applications. More attention should be paid on the disposal and utilization of the harvested mixture of algal and flocculating microbial biomass.

•A simplified two-dimensional model is proposed.•The flow maldistribution of a PCHE plate is investigated.•Backflows, vortex and thermo-properties result in differences between two models.•Mass flow rate of 0.45 g/s presents the most even flow distribution.•The proposed simplified model can meet the requirement of engineering accuracy.

Porphyrin assemblies have controllable morphology, high biocompatibility, and good optical properties and were widely used in biomedical diagnosis and treatment. With the development of DNA biotechnology, combining DNA with porphyrin assemblies can broaden the biological applications of porphyrins. Porphyrin assemblies can serve as nanocarriers for DNA, although the fundamental interactions between them are not well understood. In this work, zinc meso-tetra(4-pyridyl)porphyrin (ZnTPyP) assemblies were prepared in the presence of various surfactants and at different pH values, yielding a variety of aggregation forms. Among them, the hexagonal stacking form exposes more pyridine substituents, and the hydrogen bonding force between the substituents and the DNA bases allows the DNA to be quickly adsorbed on the surface of the assemblies. The effects of DNA sequence and length were systematically tested. In particular, the adsorption of duplex DNA was less efficient compared to the adsorption of single-stranded DNA. This fundamental study is useful for the further combination of DNA and porphyrin assemblies to prepare new functional hybrid nanomaterials.

Background: Aging, noise, infection, and ototoxic drugs are the major causes of human acquired sensorineural hearing loss, but treatment options are limited. CRISPR/Cas9 technology has tremendous potential to become a new therapeutic modality for acquired non-inherited sensorineural hearing loss. Here, we develop CRISPR/Cas9 strategies to prevent aminoglycoside-induced deafness, a common type of acquired non-inherited sensorineural hearing loss, via disrupting the Htra2gene in the inner ear which is involved in apoptosis but has not been investigated in cochlear hair cell protection. Results: The results indicate that adeno-associated virus (AAV)-mediated delivery of CRISPR/SpCas9 system ameliorates neomycin-induced apoptosis, promotes hair cell survival, and significantly improves hearing function in neomycin-treated mice. The protective effect of the AAV–CRISPR/Cas9 system in vivo is sustained up to 8 weeks after neomycin exposure. For more efficient delivery of the whole CRISPR/Cas9 system, we also explore the AAV–CRISPR/SaCas9 system to prevent neomycin-induced deafness. The in vivo editing efficiency of the SaCas9 system is 1.73% on average. We observed significant improvement in auditory brainstem response thresholds in the injected ears compared with the non-injected ears. At 4 weeks after neomycin exposure, the protective effect of the AAV–CRISPR/SaCas9 system is still obvious, with the improvement in auditory brainstem response threshold up to 50 dB at 8 kHz. Conclusions: These findings demonstrate the safe and effective prevention of aminoglycoside-induced deafness via Htra2gene editing and support further development of the CRISPR/Cas9 technology in the treatment of non-inherited hearing loss as well as other non-inherited diseases.